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and IL-12 by endogenous IL-10 in progressive MS
From the Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA.
Address correspondence and reprint requests to Dr. Howard L. Weiner, Center for Neurologic Diseases, Brigham and Women’s Hospital, 77 Avenue Louis Pasteur, HIM-730, Boston, MA 02115-5817; e-mail: weiner{at}cnd.bwh.harvard.edu
BACKGROUND: MS is a chronic inflammatory disease of the CNS postulated to be a Th1 type cell–mediated autoimmune disease. There is increased interferon-
(IFN) secretion in MS, and IFN administration induces exacerbations of disease. IFN expression is closely regulated by a number of cytokines produced by different cells of the immune system. Interleukin-12 (IL-12) is a major factor leading to Th1-type responses, including IFN secretion, and there is increased secretion of IL-12 in MS. IL-10 is a potent inhibitor of both IL-12 and IFN expression.
METHODS: The authors investigated cytokine production and proliferative responses of peripheral blood mononuclear cells stimulated with soluble anti-CD3 in healthy controls and patients with stable relapsing-remitting MS or progressive MS.
RESULTS: The authors found that T cell receptor–mediated IFN and IL-10 secretion were increased in progressive MS, whereas IL-4 and IL-2 secretion and lymphocyte proliferative responses were normal. Anti–IL-12 antibody suppressed raised IFN in progressive MS but did not affect raised IL-10. In addition, neutralization of endogenous IL-10 upregulated IFN in controls but not progressive MS. IL-10 was produced by CD4+ cells whereas IFN was produced by both CD4+ and CD8+ cells. There were no differences in IL-10 receptor expression in MS patients.
CONCLUSIONS: These abnormalities in IL-10 regulation were not seen in the relapsing-remitting form of MS. Thus, the defect in regulation of both IL-12 and IFN production by endogenous IL-10 in progressive MS could be an important factor involved in the transition of MS from the relapsing to the progressive stage and has implications for treating MS patients with exogenous IL-10.
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